Brentuximab Vedotin Granted FDA Approval for pcALCL, Mycosis Fungoides
Drug approval was granted based on data from a phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials.
The US Food and Drug Administration (FDA) granted regular approval to brentuximab vedotin (Adcetris) for 2 indications: primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF), in adults who have received prior systemic therapy. Originally granted breakthrough therapy designation, orphan designation, and priority review for these indications, this regular approval was based on data from the phase 3 ALCANZA trial and 2 phase 2 investigator-sponsored trials.1,2
Primary cutaneous ALCL and MF are the most common subtypes of cutaneous T-cell lymphoma (CTCL), an incurable, often disfiguring, rare blood cancer of the skin. CTCL manifests as red, scaly patches or thickened plaques of skin, often mimicking eczema or chronic dermatitis. Treatment options for patients with CTCL are limited.
Brentuximab vedotin is an antibody-drug conjugate comprising an anti-CD30 monoclonal antibody attached to a microtubule disrupting agent (monomethyl auristatin E). The recommended dose is 1.8 mg/kg, to a maximum of 180 mg, IV infusion over 30 minutes every 3 weeks for a maximum of 16 cycles or until disease progression or unacceptable toxicity.
The phase 3 ALCANZA trial was an open-label, multicenter clinical trial in which 131 patients were randomized 1:1 to receive brentuximab vedotin monotherapy or physician's choice of methotrexate or bexarotene. The primary end point of the ALCANZA trial was achieved with a highly statistically significant improvement in the rate of objective response lasting at least 4 months (ORR4) in patients in the treatment arm vs the physician's choice arm (56.3% vs 12.5%).
Key secondary end points included objective response rate, 67.2% vs 20.3%; complete response rate, 15.6% vs 1.6%; and median progression-free survival, 16.7 months vs 3.5 months, in the treatment vs physician's choice arms, respectively.
The safety profile was consistent with the existing prescribing information. The most common adverse events (reported by 20% or more of patients) included anemia, diarrhea, fatigue, nausea, neuropathy, neutropenia, and peripheral sensory neuropathy.
Data from the 2 investigator-sponsored phase 2 trials involving 73 patients with MF, represented a broader spectrum of CD30-expression levels than in the ALCANZA trial, and were also incorporated into the supplemental Biologics License Application.
This is the fourth FDA-approved indication for this agent. Full prescribing information is available at www.accessdata.fda.gov/drugsatfda_docs/label/2017/125388s094lbl.pdf.
1. Seattle Genetics announces FDA approval of Adcetris® (brentuximab vedotin) for primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) [news release]. Bothell, WA: Seattle Genetics Inc; November 9, 2017. http://www.businesswire.com/news/home/20171109006193/en/Seattle-Genetics-Announces-FDA-Approval-ADCETRIS%C2%AE-Brentuximab. Accessed November 9, 2017.
2. FDA approves brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma [news release]. U.S. Food & Drug Administration website. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584543.htm?utm_campaign=Oncology%2011%2F9&utm_medium=email&utm_source=Eloqua&elqTrackId=06d11c937bec44c79cd3d453daecb608&elq=063878d5859d40ec8538c4d7994344fd&elqaid=1289&elqat=1&elqCampaignId=770. Last updated November 9, 2017. Accessed November 9, 2017.